10-17693310-AA-TT

Variant names:

• chr10-17693310-AA-TT
• NM_003473.4:c.533_534delAAinsTT
• STAM p.Lys178Ile

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_003473.4(STAM):​c.533_534delAAinsTT​(p.Lys178Ile) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: STAM NM_003473.4 missense, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.32
• Publications: 0 publications found

Genes affected

STAM (HGNC:11357): (signal transducing adaptor molecule) This gene encodes a member of the signal-transducing adaptor molecule family. These proteins mediate downstream signaling of cytokine receptors and also play a role in ER to Golgi trafficking by interacting with the coat protein II complex. The encoded protein also associates with hepatocyte growth factor-regulated substrate to form the endosomal sorting complex required for transport-0 (ESCRT-0), which sorts ubiquitinated membrane proteins to the ESCRT-1 complex for lysosomal degradation. Alternatively spliced transcript variants have been observed for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003473.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	NM_003473.4	MANE Select	c.533_534delAAinsTT	p.Lys178Ile	missense splice_region	N/A	NP_003464.1	Q92783-1
	STAM	NM_001324282.2		c.437_438delAAinsTT	p.Lys146Ile	missense splice_region	N/A	NP_001311211.1
	STAM	NM_001324283.2		c.383_384delAAinsTT	p.Lys128Ile	missense splice_region	N/A	NP_001311212.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STAM	ENST00000377524.8	TSL:1 MANE Select	c.533_534delAAinsTT	p.Lys178Ile	missense splice_region	N/A	ENSP00000366746.3	Q92783-1
	STAM	ENST00000892730.1		c.533_534delAAinsTT	p.Lys178Ile	missense splice_region	N/A	ENSP00000562789.1
	STAM	ENST00000945545.1		c.533_534delAAinsTT	p.Lys178Ile	missense splice_region	N/A	ENSP00000615604.1

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-17735309;